Research on neuroprotective effects of a fusion protein of omega-conotoxin mviia and thioredoxin

Abstract

Ischemic stroke is one of the most dangerous human diseases. Blood supply to the brain is decreased initiating the ischemic cascade with the consequence of a Ca²⁺ influx into nerve-cells. This Ca²⁺ influx can than cause neuronal injury or death of cells. Omega-conotoxin MVIIA (omega-CTX) is a neurotoxin isolated from the venom of Cone snail Conus magus. It is a potent selective blocker of the N-type voltage-sensitive calcium channel in neurons and therefore has the potential to promote neuroprotection through inhibition of Ca²⁺ influx into nerve-cells. Omega-CTX has been cloned, expressed in the fusion form with thioredoxin (Trx-CTX ) in E. coli in the institute of biotechnology, Hanoi. In this paper we present our study on neuroprotectiv activity of Trx-CTX in mouse model of global cerebral ischemia and focal brain ischemia. The experiments were carried out in male mice of Swiss race weighing 40 g. Trx-CTX were injected i.v. in the model of global cerebral ischemia, one time with a dose of 5 or 10 mg/kg and in the other model two times, each with a dose of 5 mg/kg. The results showed that in global cerebral ischemia Trx-CTX has decreased neuronal injury and death of CA1 cells of dorsal hippogampus. In other model Trx-CTX also decreased infarction size of the ischemic brain. Trx-CTX proof to possess neuroprotective effect and could be used in further researchs for medicinal purpose.